Evaluation of Drug Crystallinity in Aqueous Suspension Using Terahertz Time‐Domain Attenuated Total Reflection Spectroscopy

Terahertz pulsed spectroscopy has recently been demonstrated to be a novel technique for the investigation of the solid‐state properties of pharmaceutical materials. In this study, we directly measured the crystallinity of a drug suspended in water, using a terahertz pulsed attenuated total reflection (ATR) method. The dihydropyridine calcium channel blocker nifedipine is classified as a poorly soluble drug; its most stable crystalline form is known as form I. Transmission spectra, collected from 0.2 to 2.0 THz (6.6 to 66 cm−1), of nifedipine crystals had a strong absorption peak at 1.2 THz (40 cm−1) at room temperature. When the nifedipine crystals were mixed with poloxamer 188 and suspended in water, the resulting spectra measured using the ATR method had a peak at the same frequency as in the spectra obtained in transmission mode. Furthermore, the peak area was proportional to the amount of crystals. The upward sloping baseline in the spectra, corresponding to water absorption, decreased stepwise with increasing amounts of crystalline particles. We confirmed that the spectra gave excellent quantitative results, using partial least‐squares regression analysis. The results suggest the possibility of using this method for qualitative and quantitative assessments of crystalline drugs in suspension. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4065-4071, 2013